Association of shorter mean telomere length with large artery stiffness in patients with coronary heart disease

Wang, Yunying; Chen, Aifang; Wang, Huazhang; Xie, Li; Sui, Kexu; Zhang, Qiyi

doi:10.3109/13685538.2010.529196

Cited by 42 publications

(28 citation statements)

References 25 publications

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“…The Sikh males had significantly shorter mean RTL compared to Sikh females, P =0.014. These findings are in agreement with several previous studies from multiple ethnic populations reporting presence of shorter RTL associated with age-related cardiometabolic diseases including T2D, insulin resistance, MI, and CHD 31,43, 44 , containing three previous studies on South Asians 12 , 21, 45 . We also report discovery of a novel signal represented by an intronic variant in CSNK2A2 gene associated with shorter RTL ( P =4.52×10 −8 ) in Punjabi Sikhs (Supplementary Figure 4).…”

Section: Discussionsupporting

confidence: 93%

“…In addition, mean RTL showed a gradual decline from healthy subjects (with no disease) to individuals with T2D and CHD showing respective mean RTL of 2.67± 0.16 in healthy, 2.08±0.14 in CHD, 1.83±0.34 in T2D, and 0.77±0.14 in T2D+CHD individuals showing highly significant difference between healthy subjects versus T2D and CHD patients ( P =3×10 −15 ) (Figure 5). Mean RTL levels were also significantly lower ( P =0.014) in Sikh males (1.82±0.11) compared with females (2.29±0.15), irrespective of the disease status, consistent with observations in South Asians and other ethnic groups 21, 31, 43, 44 (Supplementary Figure 2). …”

Section: Resultssupporting

confidence: 85%

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Genome-Wide Association Study Identifies Variants in Casein Kinase II ( CSNK2A2 ) to be Associated With Leukocyte Telomere Length in a Punjabi Sikh Diabetic Cohort

Saxena

Bjonnes

Prescott

et al. 2014

Circ Cardiovasc Genet

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Background Telomere length is a heritable trait and short telomere length has been associated with multiple chronic diseases. We investigated the relationship of relative leukocyte telomere length (RTL) with cardiometabolic risk and performed the first GWAS and meta-analysis to identify variants influencing RTL in a population of Sikhs from South Asia. Methods and Results Our results revealed a significant independent association of shorter RTL with type 2 diabetes (T2D) and heart disease. Our discovery GWAS (n=1,616) was followed by Stage 1 replication of 25 top signals (P<10−6) in an additional Sikhs (n=2,397). On combined discovery and Stage 1 meta-analysis (n= 4013), we identified a novel RTL locus at chromosome 16q21 represented by an intronic variant (rs74019828) in the CSNK2A2 gene (β −0.38, P=4.5×10−8). We further tested 3 top variants by genotyping in UKCVD (Caucasians n=2,952) for Stage 2. Next we performed in silico replication of 139 top signals (p<10−5) in UKTWIN, NHS, PLCO and MDACC (n=10,033) and joint meta-analysis (n=16,998). The observed signal in CSNK2A2 was confined to South Asians and could not be replicated in Caucasians due to significant difference in allele frequencies (P<0.001). CSNK2A2 phosphorylates TRF1 and plays an important role for regulation of telomere length homoeostasis. Conclusions By identification of a novel signal in telomere pathway genes, our study provides new molecular insight into the underlying mechanism that may regulate telomere length and its association with human aging and cardiometabolic pathophysiology.

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Section: Discussionsupporting

confidence: 93%

Section: Resultssupporting

confidence: 85%

Genome-Wide Association Study Identifies Variants in Casein Kinase II ( CSNK2A2 ) to be Associated With Leukocyte Telomere Length in a Punjabi Sikh Diabetic Cohort

Saxena

Bjonnes

Prescott

et al. 2014

Circ Cardiovasc Genet

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“…Furthermore, cross-sectional studies have shown that a shorter TL is associated with measures of vascular stiffness, including increased aPWV and reduced carotid distensibility (Benetos et al 2001;Nawrot et al 2010;Wang et al 2011). However, other cross-sectional studies have reported no association between TL and arterial stiffness in females (Benetos et al 2001) and in diabetics (Tentolouris et al 2007).…”

Section: Mcdonnellmentioning

confidence: 99%

“…Two recent meta-analyses have demonstrated that telomere shortening is related to CV (Haycock et al 2014) and metabolic outcomes (D'Mello et al 2015), although there was significant heterogeneity in observations within these studies. Interestingly, previous studies have also reported significant cross-sectional associations between TL and measures of vascular stiffness (Benetos et al 2001;Nawrot et al 2010;Wang et al 2011) and a recent longitudinal study illustrated that a faster rate of telomere shortening was associated with increased carotid intima-media thickness, independent of traditional CV risk factors (Masi et al 2014), leading to the hypothesis that telomere shortening provides a cellular and genetic link to vascular ageing. However, observational studies conducted mostly in middle-aged and older adults have shown weak or no relationship between TL and chronological age, vascular stiffness or CV disease (Tentolouris et al 2007;De Meyer et al 2012;Morgan et al 2014).…”

Section: Introductionmentioning

confidence: 98%

The age dependent association between aortic pulse wave velocity and telomere length

McDonnell

Butcher

Cockcroft

et al. 2014

Journal of the American Society of Hypertension

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Key pointsr Age significantly modifies the relationship between aortic pulse wave velocity and telomere length.r The differential relationships observed between aortic pulse wave velocity and telomere length in younger and older individuals suggest that the links between cellular and vascular ageing reflect a complex interaction between genetic and environmental factors acting over the life-course.Abstract Ageing is associated with marked large artery stiffening. Telomere shortening, a marker of cellular ageing, is linked with arterial stiffening. However, the results of existing studies are inconsistent, possibly because of the confounding influence of variable exposure to cardiovascular risk factors. Therefore, we investigated the relationship between telomere length (TL) and aortic stiffness in well-characterized, younger and older healthy adults, who were pre-selected on the basis of having either low or high aortic pulse wave velocity (aPWV), a robust measure of aortic stiffness. Demographic, haemodynamic and biochemical data were drawn from participants in the Anglo-Cardiff Collaborative Trial. Two age groups with an equal sex ratio were examined: those aged <30 years (younger) or >50 years (older). Separately for each age group and sex, DNA samples representing the highest (n = 125) and lowest (n = 125) extremes of aPWV (adjusted for blood pressure) were selected for analysis of leukocyte TL. Ultimately, this yielded complete phenotypic data on 904 individuals. In younger subjects, TL was significantly shorter in those with high aPWV vs. those with low aPWV (P = 0.017). By contrast, in older subjects, TL was significantly longer in those with high aPWV (P = 0.001). Age significantly modified the relationship between aPWV and TL (P < 0.001). Differential relationships are observed between aPWV and TL, with an inverse association in younger individuals and a positive association in older individuals. The links between cellular and vascular ageing reflect a complex interaction between genetic and environmental factors acting over the life-course. Abbreviations aPWV, aortic pulse wave velocity; BMI, body mass index; CRP, C-reactive protein; CV, cardiovascular; HDL, high-density lipoprotein; MAP, mean arterial pressure; T/S, telomere/standard; TL, telomere length. * These authors contributed equally to this work.

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“…Several studies have suggested relationships between telomere length and cardiovascular diseases, although the associations varied across studies [34][35][36][37][38], while associations between the misregulation of telomere length and diabetes have also been reported [39][40][41].…”

mentioning

confidence: 99%

Genetic and epigenetic trends in telomere research: a novel way in immunoepigenetics

Melicher

Buzás

Falus

2015

Cell. Mol. Life Sci.

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Telomeres are protective heterochromatic structures that cap the end of linear chromosomes and play a key role in preserving genomic stability. Telomere length represents a balance between processes that shorten telomeres during cell divisions with incomplete DNA replication and the ones that lengthen telomeres by the action of telomerase, an RNA-protein complex with reverse transcriptase activity which adds telomeric repeats to DNA molecule ends. Telomerase activity and telomere length have a crucial role in cellular ageing and in the pathobiology of several human diseases attracting intense research. The last few decades have witnessed remarkable advances in our understanding about telomeres, telomere-associated proteins, and the biogenesis and regulation of the telomerase holoenzyme complex, as well as about telomerase activation and the telomere-independent functions of telomerase. Emerging data have revealed that telomere length can be modified by genetic and epigenetic factors, sex hormones, reactive oxygen species and inflammatory reactions. It has become clear that, in order to find out more about the factors influencing the rate of telomere attrition in vivo, it is crucial to explore both genetic and epigenetic mechanisms. Since the telomere/telomerase assembly is under the control of multiple epigenetic influences, the unique design of twin studies could help disentangle genetic and environmental factors in the functioning of the telomere/telomerase system. It is surprising that the literature on twin studies investigating this topic is rather scarce. This review aims to provide an overview of some important immune response- and epigenetics-related aspects of the telomere/telomerase system demanding more research, while presenting the available twin data published in connection with telomere research so far. By emphasising what we know and what we still do not know in these areas, another purpose of this review is to urge more twin studies in telomere research.

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Association of shorter mean telomere length with large artery stiffness in patients with coronary heart disease

Cited by 42 publications

References 25 publications

Genome-Wide Association Study Identifies Variants in Casein Kinase II ( CSNK2A2 ) to be Associated With Leukocyte Telomere Length in a Punjabi Sikh Diabetic Cohort

Genome-Wide Association Study Identifies Variants in Casein Kinase II ( CSNK2A2 ) to be Associated With Leukocyte Telomere Length in a Punjabi Sikh Diabetic Cohort

The age dependent association between aortic pulse wave velocity and telomere length

Genetic and epigenetic trends in telomere research: a novel way in immunoepigenetics

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